Lung disease, including airway diseases that affect lung function, includes asthma, obstructive pulmonary disease, emphysema, pneumonia, tuberculosis, lung cancer, pulmonary fibrosis, sarcoidosis, HIV/AIDS-related lung disease, alpha-1 antitrypsin deficiency, respiratory distress syndrome, bronchopulmonary dysplasia, embolism, and chronic obstructive pulmonary disease (COPD), among others.
COPD is the fourth leading cause of morbidity and mortality in the United States and is expected to rank third as the cause of death worldwide by 2020 (1). Cigarette smoking is widely recognized as a primary causative factor of COPD and accounts for approximately 80-90% of all cases in the United States (2). It has been estimated that up to 25-50% of cigarette smokers may develop CORD, and its prevalence increases with age (1-4).
The pulmonary component of CORD is primarily characterized by chronic airway inflammation and incompletely reversible, usually progressive, airflow obstruction (5, 1). The operational diagnosis of CORD has traditionally been made by spirometry, as a ratio of the forced expiratory volume in one second (FEV1) to the forced vital capacity (FVC) below 70% (1). Pathophysiological mechanisms believed to underlie CORD include an imbalance between proteinase and anti-proteinase activity in the lung, dysregulation of anti-oxidant activity and chronic abnormal inflammatory response to long-term exposure to noxious gases or particles leading to the destruction of the lung alveoli and connective tissue (5, 1). However, CORD is increasingly recognized as a syndrome associated with significant systemic effects which are attributed to low-grade, chronic systemic inflammation (6, 7, 8, 9).
Conventional methods of diagnosing lung disease such as COPD employ diagnostic tests which rely on the presumed correlation of decreased pulmonary function with the presence of lung disease such as COPD, asthma, fibrosis, emphysema and others. Spirometry, which is the most commonly performed lung function test measures the quantity of air that a subject can exhale and the speed with which the air is exhaled. While lung function tests can provide a general assessment of the functional status of a subject's lungs, they do not distinguish between the different types of lung diseases that may be present. Certain lung related diseases cannot be confirmed based on functional tests alone. In addition, such tests assist in the diagnosis of lung disease only when an abnormality in lung function already exists. Functional diagnostic methods at a single time point also do not predict the rate of progression of the disease.
In contrast to functional diagnostic methods, assessment of protein/peptide biomarkers can be used as diagnostic as well as prognostic indicators of the progression (e.g., predicted rate of progression) of a disease. Thus, the identification of proteins, such as those found in plasma, whose abundance and/or structure is altered in individuals with lung disease can be used to diagnose the presence of disease, provide a prognosis for an individual with lung disease (i.e., predicted rate of progression), and provides a better understanding of biological mechanisms underlying a disease.